Re-analysis of a human hepatitis B virus (HBV) isolate from an East African wild born Pan troglodytes schweinfurthii : Evidence for interspecies recombination between HBV infecting chimpanzee and human Emmanuil N. Magiorkinis, Gkikas N. Magiorkinis, Dimitrios N. Paraskevis, Angelos E. Hatzakis * National Retrovirus Reference Center, Department of Hygiene and Epidemiology, University of Athens, School of Medicine, Mikras Asias 75, GR-11527, Athens, Greece Received 9 September 2004; received in revised form 22 November 2004; accepted 15 December 2004 Available online 10 March 2005 Received by G. Pesole Abstract According to current estimates, hepatitis B virus (HBV) has infected 2 billion people worldwide and among them, 360 million suffer from chronic HBV infection. Except humans, HBV or HBV-like viruses have also been isolated from different species of apes and mammals. Although recombination has been described to occur extensively between different genotypes within the human HBV lineage, no recombination event has ever been reported between human and non-human primate HBV sequences. It was our objective to perform an exhaustive search for recombination between human and non-human primate HBV strains among all available full-length human and non- human primate HBV sequences, using bootscanning and phylogenetic analyses. Intriguingly, we found that an HBV sequence isolated from a wild born Pan troglodytes schweinfurthii in East Africa–FG–is a recombinant consisting of HBV infecting chimpanzee (ChHBV) and human genotype C. More specifically, in a fragment of approximately 500 nt (positions 551–1050 spanning half of the RT domain of pol , which overlaps with half of the coding region of the small surface protein), FG grouped with HBV genotype C, while in the rest of the genome it grouped with ChHBV sequences. Phylogenetic analyses showed that in the latter region FG was more closely related to the Pan troglodytes troglodytes subspecies, forming an outlier to this group. Moreover, we show evidence that the recombination event occurred after the initial dispersion of HBV genotype C in humans. Finally, our findings point out that although rare recombination between HBV viruses infecting different species occurs. D 2004 Elsevier B.V. All rights reserved. Keywords: Hepadnaviruses; Mosaic; Primates; Phylogenetic analysis 1. Introduction Hepatitis B virus (HBV) is the prototype member of a family of viruses designated as Hepadnaviridae . This family consists of enveloped DNA viruses with a partially double-stranded genome of approximately 3182–3221 nt in length. HBV sequences isolated from humans have been classified into eight genotypes A–H (Norder et al., 1994; Stuyver et al., 2000; Okamoto et al., 1988; Arauz-Ruiz et al., 2002). The distribution of human HBV genotypes 0378-1119/$ - see front matter D 2004 Elsevier B.V. All rights reserved. doi:10.1016/j.gene.2004.12.021 Abbreviations: ChHBV, chimpanzee hepatitis B virus; G, gamma; GiHBV, gibbons hepatitis B virus; GTR, general time reversible model; HBV, hepatitis B virus; HBV-DNA, hepatitis B virus DNA; HBsAg, hepatitis B virus surface antigen; MC, Monte Carlo; ML, maximum likelihood; OuHV, orang-utan hepatitis virus; pol, polymerase gene; RT, reverse transcriptase; SHBs, small hepatitis B virus surface protein; WMHBV, woolly monkey hepatitis B virus. * Corresponding author. Tel.: +30 210 7462090; fax: +30 210 7462190. E-mail address: ahatzak@med.uoa.gr (A.E. Hatzakis). Gene 349 (2005) 165 – 171 www.elsevier.com/locate/gene